TY - JOUR
T1 - Molecular characterization of Novel ATM fusions in chronic lymphocytic leukemia and T-cell prolymphocytic leukemia
AU - Kanagal-Shamanna, Rashmi
AU - Bao, Haiyan
AU - Kearney, Hutton
AU - Smoley, Stephanie
AU - Tang, Zhenya
AU - Luthra, Rajyalakshmi
AU - Yang, Hui
AU - Zhang, Shanshan
AU - Lin, Pei
AU - Wu, Depei
AU - Medeiros, L. Jeffrey
AU - Lu, Xinyan
N1 - Funding Information:
This work was supported in part by the institutional research grant and the leukemia SPORE career development grant awarded to R.K-S.
Publisher Copyright:
© 2021 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2022
Y1 - 2022
N2 - ATM deletions and/or mutations are recurrent in lymphoid neoplasms while rearrangements are rare. In this study, we used mate pair sequencing (MPseq) technology to characterize two novel ATM rearrangements in one patient with chronic lymphocytic leukemia (CLL) and one patient with T-prolymphocytic leukemia (T-PLL). Both patients showed chromosome 11q22 aberrations encompassing ATM by conventional karyotype and fluorescence in situ hybridization: isolated t(11;13)(q22;q14) in CLL and a complex karyotype with apparent 11q deletion and unbalanced der(14)t(11;14)(q22;p11.2) in T-PLL. MPseq identified ATM-LINC00371 fusion in CLL and ATM-USP28 in T-PLL, both of which led to ATM inactivation, confirmed by loss of immunohistochemical protein expression. Next-generation sequencing mutation analysis detected concurrent ATM mutation(s) CLL patient, while T-PLL lacked ATM mutation. ATM rearrangements, not apparently detectable using standard laboratory technologies, represent another mechanism of loss-of-function. Recent high-throughput technologies such as MPseq can uncover novel pathogenic gene fusions and resolve complex chromosomal rearrangements in hematologic malignancies.
AB - ATM deletions and/or mutations are recurrent in lymphoid neoplasms while rearrangements are rare. In this study, we used mate pair sequencing (MPseq) technology to characterize two novel ATM rearrangements in one patient with chronic lymphocytic leukemia (CLL) and one patient with T-prolymphocytic leukemia (T-PLL). Both patients showed chromosome 11q22 aberrations encompassing ATM by conventional karyotype and fluorescence in situ hybridization: isolated t(11;13)(q22;q14) in CLL and a complex karyotype with apparent 11q deletion and unbalanced der(14)t(11;14)(q22;p11.2) in T-PLL. MPseq identified ATM-LINC00371 fusion in CLL and ATM-USP28 in T-PLL, both of which led to ATM inactivation, confirmed by loss of immunohistochemical protein expression. Next-generation sequencing mutation analysis detected concurrent ATM mutation(s) CLL patient, while T-PLL lacked ATM mutation. ATM rearrangements, not apparently detectable using standard laboratory technologies, represent another mechanism of loss-of-function. Recent high-throughput technologies such as MPseq can uncover novel pathogenic gene fusions and resolve complex chromosomal rearrangements in hematologic malignancies.
KW - ATM fusion
KW - ATM rearrangement
KW - CLL
KW - MPseq
KW - T-PLL
KW - mate-pair sequencing
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U2 - 10.1080/10428194.2021.2010061
DO - 10.1080/10428194.2021.2010061
M3 - Article
C2 - 34898335
AN - SCOPUS:85121367670
SN - 1042-8194
VL - 63
SP - 865
EP - 875
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 4
ER -